Nuclear Tau, a Key Player in Neuronal DNA Protection

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2010 Dec 7

PMID 21131359

Citations 200

Authors

Audrey Sultan

Fabrice Nesslany

Marie Violet

Severine Begard

Anne Loyens

Smail Talahari

Zeyni Mansuroglu

Daniel Marzin

Nicolas Sergeant

Sandrine Humez

Morvane Colin

Eliette Bonnefoy

Luc Buee

Marie-Christine Galas

Affiliations

Soon will be listed here.

Abstract

Tau, a neuronal protein involved in neurodegenerative disorders such as Alzheimer disease, which is primarily described as a microtubule-associated protein, has also been observed in the nuclei of neuronal and non-neuronal cells. However, the function of the nuclear form of Tau in neurons has not yet been elucidated. In this work, we demonstrate that acute oxidative stress and mild heat stress (HS) induce the accumulation of dephosphorylated Tau in neuronal nuclei. Using chromatin immunoprecipitation assays, we demonstrate that the capacity of endogenous Tau to interact with neuronal DNA increased following HS. Comet assays performed on both wild-type and Tau-deficient neuronal cultures showed that Tau fully protected neuronal genomic DNA against HS-induced damage. Interestingly, HS-induced DNA damage observed in Tau-deficient cells was completely rescued after the overexpression of human Tau targeted to the nucleus. These results highlight a novel role for nuclear Tau as a key player in early stress response.

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